Acute graft versus host disease (aGvHD) is a severe and potentially fatal complication of allogeneic hematopoietic stem cell transplantation (HCT). The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for severe aGvHD as early as 7 days after HCT based on 2 serum biomarkers, suppressor of tumorigenesis 2 (ST2) and regenerating islet-derived 3α (Reg3α). Patients who consent to this study will have their blood tested weekly up to four times within the first month post HCT to determine if they are at high risk for severe GVHD based on MAP. Patients who are at high risk at any of these four tests will be treated with methylprednisolone to see if it prevents the development of severe aGvHD. Methylprednisolone starts with the dose of 2 mg/kg for 5 days. If no signs of aGvHD, the dose of methylprednisolone is gradually tapered within the following 16 days. Patients will be followed for the development of severe aGvHD for up to 3 months from the HCT and will continue to be followed at routine clinic visits for up to one year after HCT.

Inclusion Criteria:

• Any donor type (e.g., related, unrelated, haplo) or stem cell source (bone marrow, peripheral blood, cord blood).
• Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is acceptable.
• GVHD prophylaxis must include a calcineurin inhibitor combined with post transplant cyclophosphamide.
• The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3 post-HCT is permitted
• Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment.
• ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days prior to enrollment.
• Signed and dated written informed consent obtained from patient or legal representative.

Exclusion Criteria:

• Patients who develop acute GVHD prior to start of study drug
• Patients at very high risk for relapse post HCT as defined by very high disease risk index
• Patients participating in a clinical trial where prevention of GVHD is the primary endpoint
• Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
• Patients who are pregnant
• Patients on dialysis within 7 days of enrollment
• Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2 within 14 days of enrollment.
• Patients receiving investigational agent within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of methylprednisolone.